COBRE: NE CREIGHTON U: P2: NEUROGULINS IN MYELIN REPAIR IN CNS & PNS

COBRE：NE CREIGHTON U：P2：中枢神经系统髓磷脂修复中的神经调节蛋白

• 批准号: 7960540
• 负责人: KRISTEN M DRESCHER
• 金额: $ 8.9万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960540
• 关键词: Address; Centers of Research Excellence; Charcot-Marie-Tooth Disease; Computer Retrieval of Information on Scientific Projects Database; Demyelinations; Diabetes Mellitus; Disease; Epidermal Growth Factor; Family member; Funding; Genetic; Goals; Grant; Human; In Vitro; Infection; Injury; Institution; Knowledge; Literature; Mediating; Molecular Biology; Mus; Myelin; Neuraxis; Neuregulins; Pathology; Peripheral; Peripheral Nervous System; Peripheral Nervous System Diseases; Process; Proteins; Research; Research Personnel; Resources; Role; Signal Transduction; Signaling Molecule; Source; Spinal Cord; System; Testing; United States National Institutes of Health; Viral Vector; Virus; axonopathy; in vivo; in vivo Model; insight; member; myelination; myelinopathy; neurosurgery; novel strategies; repaired; response; sciatic nerve; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. No body of literature examines the role of neuregulins, members of the epidermal growth factor superfamily, and their signaling molecules (erb family members) in response to in vivo virus-induced pathology, although they are known to be upregulated following injury to the peripheral nervous system. The studies in this proposal will examine the processes involved in the repair of the central and peripheral nervous systems (CNS, PNS respectively) following virus-induced damage to the myelin of the spinal cord and sciatic nerves. Thus, this proposal represents a novel approach to studying these proteins, and success in any of the specific aims would significantly enhance our knowledge of the PNS and CNS. In this application, we will test the hypothesis that neuregulins protect the CNS and PNS from Theiler¿s virus-induced pathology by enhancing myelination processes via erbB signaling. The following specific aims will be addressed in this application: 1) Test the hypothesis that neuregulin is upregulated in the central and peripheral nervous systems following TMEV-mediated insult. 2) Develop in vitro and in vivo models to test the hypothesis that increased erb-B2 signaling enhances myelination in the CNS and PNS. This specific aim will utilize 3 approaches: first, we will develop organotypic cultures of spinal cords and sciatic nerves and alter neuregulins in vitro to determine the effects on demyelination; second, we will develop targeted erb-B2 conditional over-expressing mice, and finally, we will use a viral vector to deliver neuregulin in vivo to virus infected mice. Peripheral neuropathies in humans have been attributed to both genetic (e.g. Charcot-Marie-Tooth disease) and environmental (e.g., diabetes) causes. Two pathologies can be observed in this condition, axonopathy or myelinopathy. Each of the specific aims will provide us with insights into the processes involved in maintaining / repairing myelin in the peripheral and central nervous systems following infection. Our long-term goal is to explore the possibilities of intervening in the demyelinating processes and alleviating the complications associated with these diseases.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 没有文献研究神经调节蛋白，表皮生长因子超家族成员，及其信号分子（erb家族成员）在体内病毒诱导的病理反应中的作用，尽管已知它们在外周神经系统损伤后上调。本提案中的研究将检查病毒诱导的脊髓和坐骨神经髓鞘损伤后中枢和外周神经系统（分别为CNS和PNS）的修复过程。因此，这一建议代表了一种新的方法来研究这些蛋白质，并在任何特定目标的成功将显着提高我们的知识PNS和CNS。 在本申请中，我们将测试神经调节蛋白通过erbB信号增强髓鞘形成过程来保护CNS和PNS免受泰勒病毒诱导的病理的假设。在本申请中将解决以下具体目的：1）检验神经调节蛋白在TMEV介导的损伤后在中枢和外周神经系统中上调的假设。 2)开发体外和体内模型，以测试增强erb-B2信号传导增强CNS和PNS髓鞘形成的假设。这一具体目标将利用3种方法：首先，我们将开发脊髓和坐骨神经的器官型培养物，并在体外改变neuregulins以确定对脱髓鞘的影响;其次，我们将开发靶向erb-B2条件性过表达小鼠，最后，我们将使用病毒载体将neuregulin体内递送给病毒感染的小鼠。人类的周围神经病已被归因于遗传（例如Charcot-Marie-Tooth病）和环境（例如，糖尿病）的原因。在这种情况下可以观察到两种病理，轴突病或髓鞘病。每一个具体的目标将为我们提供深入了解在感染后维持/修复周围和中枢神经系统髓鞘的过程。我们的长期目标是探索干预脱髓鞘过程和减轻与这些疾病相关的并发症的可能性。